The need for general tools to admit facile query of the collection of information in the Protein Database has become of significant interest not only within the community of structural biology but also within the community of molecular biologists interested in using structure to elucidate sequence and structure-function relationships. While tools have been developed to implement database queries to find similar protein substructures or similar 3D constellations of residues, to date no general tools have been developed to implement queries based on similarity between protein surfaces. This seems an egregious omission: it is the shape and properties of the protein surface which impart its lock- and-key specificity and are hence responsible for function. A suite of tools for the three dimensional query, superposition, and analysis of protein surfaces would find a plethora of practical applications (outlined below), and would significantly enhance the practical value of the collection of protein structures in the Protein Database. It is the purpose of this proposal to develop such capabilities, admitting queries, visualization, and analyses of protein surfaces in terms of steric and biochemical properties. Starting points for the work will consist of the Primary Topographical Sketch for feature recognition which is well- developed in the field of Computer Vision, and the collection of biochemical surface analysis and visualization tools assembled into the popular program GRASP developed at Columbia University. Software and database tools developed in the course of this work will be commercialized. PROPOSED COMMERCIAL APPLICATION: The proposed surface database query capabilities are of potential commercial use the interpretation of function of gene products, in the modification of sequence to dictate specificity and function, in the design of drug molecules capable of discriminating targets in families of related proteins, and in the design of small-molecule and peptide mimetics which biochemically emulate a functional epitope on a protein surface.